Analytical Biosciences, Leiden University, PO Box 9502, Einsteinweg 55, 2300 RA, Leiden, The Netherlands,
Biogerontology. 2013 Dec;14(6):663-72. doi: 10.1007/s10522-013-9450-7. Epub 2013 Aug 15.
The role of classical lipids in aging diseases and human longevity has been widely acknowledged. Triglyceride and cholesterol concentrations are clinically assessed to infer the risk of cardiovascular disease while larger lipoprotein particle size and low triglyceride levels have been identified as markers of human longevity. The rise of lipidomics as a branch of metabolomics has provided an additional layer of accuracy to pinpoint specific lipids and its association with aging diseases and longevity. The molecular composition and concentration of lipid species determine their cellular localization, metabolism, and consequently, their impact in disease and health. For example, low density lipoproteins are the main carriers of sphingomyelins and ceramides, while high density lipoproteins are mostly loaded with ether phosphocholines, partly explaining their opposing roles in atherogenesis. Moreover, the identification of specific lipid species in aging diseases and longevity would aid to clarify how these lipids alter health and influence longevity. For instance, ether phosphocholines PC (O-34:1) and PC (O-34:3) have been positively associated with longevity and negatively with diabetes, and hypertension, but other species of phosphocholines show no effect or an opposite association with these traits confirming the relevance of the identification of molecular lipid species to tackle our understanding of healthy aging and disease. Up-to-date, a minor fraction of the human plasma lipidome has been associated to healthy aging and longevity, further research would pinpoint toward specific lipidomic profiles as potential markers of healthy aging and metabolic diseases.
经典脂质在衰老疾病和人类长寿中的作用已得到广泛认可。甘油三酯和胆固醇浓度在临床上用于推断心血管疾病的风险,而较大的脂蛋白颗粒大小和低甘油三酯水平已被确定为人类长寿的标志物。脂质组学作为代谢组学的一个分支的兴起,为确定与衰老疾病和长寿相关的特定脂质及其关联提供了额外的准确性。脂质种类的分子组成和浓度决定了它们的细胞定位、代谢,进而影响它们在疾病和健康中的作用。例如,低密度脂蛋白是神经鞘磷脂和神经酰胺的主要载体,而高密度脂蛋白主要装载醚磷酰胆碱,这部分解释了它们在动脉粥样硬化形成中的相反作用。此外,在衰老疾病和长寿中鉴定特定的脂质种类将有助于阐明这些脂质如何改变健康并影响长寿。例如,醚磷酰胆碱 PC(O-34:1)和 PC(O-34:3)与长寿呈正相关,与糖尿病和高血压呈负相关,但其他磷酰胆碱种类则没有表现出这种作用或与这些特征呈相反的关联,这证实了鉴定分子脂质种类对于我们理解健康衰老和疾病的相关性。迄今为止,人类血浆脂质组的一小部分与健康衰老和长寿有关,进一步的研究将指向特定的脂质组学特征作为健康衰老和代谢性疾病的潜在标志物。